What is the difference between gabapentin and pregabalin in terms of indications and usage?

Differences Between Gabapentin and Pregabalin: Indications and Usage

Both gabapentin and pregabalin are calcium channel α-2-δ ligands that reduce calcium influx and synaptic neurotransmitter release, but pregabalin has broader FDA-approved indications, more predictable pharmacokinetics, and potentially greater potency than gabapentin. 1

Mechanism of Action

• Both medications bind to the α-2-δ subunit of voltage-gated calcium channels, reducing calcium influx and thus decreasing synaptic neurotransmitter release into hyperexcited neurons 1
• Both are commonly used anticonvulsants for treating neuropathic pain 1

FDA-Approved Indications

Gabapentin

• Management of postherpetic neuralgia in adults 2
• Adjunctive therapy for partial onset seizures in adults and pediatric patients 3 years and older with epilepsy 2

Pregabalin

• Management of neuropathic pain associated with diabetic peripheral neuropathy 3
• Management of postherpetic neuralgia 3
• Adjunctive therapy for partial-onset seizures in patients 1 month of age and older 3
• Management of fibromyalgia 3
• Management of neuropathic pain associated with spinal cord injury 3

Pharmacokinetic Differences

• Pregabalin has more predictable linear (first-order) absorption with plasma concentrations increasing proportionately with increasing dose 4
• Gabapentin has nonlinear (zero-order) saturable absorption, making its pharmacokinetics less predictable 4
• Pregabalin reaches maximum plasma concentration within 1 hour versus 3-4 hours for gabapentin 4
• Pregabalin maintains consistent bioavailability (≥90%) regardless of dose, while gabapentin's bioavailability decreases from 60% to 33% as dosage increases from 900 to 3600 mg/day 4

Dosing Considerations

• Gabapentin: Starting dose 100-300 mg at bedtime, increasing to 900-3600 mg daily in divided doses (2-3 times daily) 1
• Pregabalin: Starting dose 50 mg three times daily or 75 mg twice daily, increasing to 150-600 mg/day in divided doses 1
• Both medications require dose adjustments in patients with renal impairment 1

Efficacy Differences

• For neuropathic pain, pregabalin 450 mg/day appears to reduce pain comparably to the predicted maximum effect of gabapentin 4
• Pregabalin may be more effective than gabapentin as an antiepileptic based on the magnitude of seizure frequency reduction 4
• Pregabalin has shown efficacy in several randomized controlled trials for painful diabetic peripheral neuropathy with an NNT of 4.04 for 600 mg/day and 5.99 for 300 mg/day 1

Side Effect Profile

• Both medications share similar side effects including dizziness, somnolence, and mental clouding 1
• Pregabalin is associated with peripheral edema, headache, and weight gain 1
• Both drugs can cause weight gain, with pregabalin showing weight gain in 14% of patients at the highest dose of 600 mg/day 5

Regulatory Status

• Pregabalin is classified as a Schedule V controlled substance under federal law due to potential for abuse 6
• Gabapentin is only classified as a controlled substance in certain states, though case reports suggest similar abuse potential 6

Clinical Considerations

• Lower starting doses are appropriate for elderly patients or those with moderate to severe renal impairment 1
• Pregabalin may be preferred for initial trials due to pharmacokinetics that support easier and more rapid titration 1
• Patients may respond to gabapentin, pregabalin, both, or neither 1

Pitfalls and Caveats

• Both medications require gradual dose titration to minimize side effects, particularly in older adults 1
• Neither medication should be stopped abruptly due to potential withdrawal symptoms 4
• Cases of visual field restriction have been reported with pregabalin in clinical trials 7
• Both medications are eliminated unchanged in urine, requiring dose adjustments with renal impairment 7